The long-term objective of these studies is to develop and characterize a mouse model of malignant melanoma that can be used to investigate tumor development, metastasis, and treatment in the primary autochthonous host as well as in syngeneic transplant recipients. We have developed a method for the induction of spontaneously metastasizing primary melanomas in C57BL/6 mice. Tumors can be induced in up to 30% of the animals. The melanomas obtained vary greatly in latent period prior to the development of the primary tumor, as well as in tumorigenicity, metastatic ability, and stability of the original phenotype. In the present application we propose to investigate spontaneous metastasis in a variety of recently induced mouse melanomas and then to evaluate selected host and tumor cell characteristics that may determine metastatic ability during tumor development. The specific aims of this work are: (1)\to trace the sequential development of metastases in selected melanomas; (2)\to determine if a relationship exists between latency, immunogenicity, and metastasis in C57BL/6 melanomas; and (3)\to identify changes in host-tumor interactions during tumor development that influence melanoma growth and metastasis. For these studies we will use extensively two melanomas induced by our method, MS and RH, because we have identified striking differences in phenotype between them. In addition, we will induce other primary melanomas to investigate the pathobiology of metastasis in the autochthonous host. We will evaluate the pattern and extent of metastasis in immunocompetent and immunosuppressed mice, evaluate immunogenicities of primary melanomas by immunization-challenge techniques, and evaluate cell-mediated immunity by tumor neutralization in vivo and cytotoxic in vitro. This new mouse melanoma system is an excellent model of spontaneous lymph node metastasis and can provide important insights into the progression and treatment of malignant melanomas. (N)